This revised application requests continuing support for a training program which provides graduate students studying for the PhD degree with broad state-of-the-art training in Systems and Integrative Biology. Students will learn and apply tools and approaches of genomics, bioinformatics, proteomics as well as cell and molecular biology to the study of integrated systems and organismic biology. The program is centered in the Department of Molecular &Integrative Physiology because of its longstanding commitment to integrative biology but students will enter from an initial year in a combined gateway Program in Biomedical Sciences (PIBS) and can be enrolled in multiple PhD programs including Physiology, Pharmacology, Neuroscience, Bioinformatics and Human Genetics. Trainees will usually be supported for two years. The potential applicant pool is all students applying to PIBS and includes both students who come to Michigan to study integrative biology and those who enter undecided and are then drawn to integrative biology. The training includes formal coursework and seminars, teaching, and research experiences with faculty in a variety of departments at the University of Michigan. All students will take graduate level courses in Integrative Biology, Cell and Molecular function, Molecular Biology and Genetics, and Computational Biology. Additional courses are selected by the student in accordance with his/her interests. Students also participate in weekly student research seminars in their PhD program which they are expected to critically evaluate the presentations of their peers. This broad training is further reinforced by each student taking a written preliminary examination at the end of the second year of study that requires and understanding of function, from the cellular and molecular level to that of the organism including interactions between the environment and the organism. A unique aspect of the proposed training is that all students will have two dissertation co-chairs, rather than the more traditional single chair, at least one of whom will be schooled in the most recent techniques in cellular, molecular, or computational biology and one being an integrative biologist. The training faculty consists of 58 outstanding scientists all of whom are expert in either cellular and molecular or systems and integrative biology and committed to training individuals to answer questions of integrative physiological relevance. PUBLIC HEALTH RELEVANCE: This training grant will increase the number of scientists trained in systems and integrative biology. This area is important as it prepares scientists to participate in translational work on health and disease.